Cox models survival analysis based on breast cancer treatments.

BACKGROUND: The aim of this study is to evaluate the association between different treatments and survival time of breast cancer patients using either standard Cox model or stratified Cox model. METHODS: The study was conducted on 15830 women diagnosed with breast cancer in British Columbia, Canada. They were divided into eight groups according to patients' ages and stage of disease Either Cox's PH model or stratified Cox model was fitted to each group according to the PH assumption and tested using Schoenfeld residuals. RESULTS: The data show that in the group of patients under age 50 years old and over age 50 with stage I cancer, the highest hazard was related to radiotherapy (HR= 3.15, CI: 1.85-5.35) and chemotherapy (HR= 3, CI: 2.29- 3.93) respectively. For both groups of patients with stage II cancer, the highest risk was related to radiotherapy (HR=3.02, CI: 2.26-4.03) (HR=2.16, CI:1.85-2.52). For both groups of patients with stage III cancer, the highest risk was for surgery (HR=0.49, CI: 0.33-0.73), (HR=0.45, CI: 0.36-0.57). For patients of age 50 years or less with stage IV cancer, none of the treatments were statistically significant. In group of patients over age 50 years old with stage IV cancer, the highest hazard was related to surgery (HR=0.64, CI: 0.53-0.78). CONCLUSION: The results of this study show that for patients with stage I and II breast cancer, radiotherapy and chemotherapy had the highest hazard; for patients with stage III and IV breast cancer, the highest hazard was associated with treatment surgery.

Influence of fluorescence on screening decisions for oral mucosal lesions in community dental practices.

BACKGROUND: Quality of oral screening examinations is dependent upon the experience of the clinician and can vary widely. Deciding when a patient needs to be referred is a critical and difficult decision for general practice clinicians. A device to aid in this decision would be beneficial. The objective of this study was to to examine the utility of direct fluorescence visualization (FV) by dental practitioners as an aid in decision-making during screening for cancer and other oral lesions. METHODS: Dentists were trained to use a stepwise protocol for evaluation of the oral mucosa: medical history, head, neck and oral exam, and fluorescent visualization exam. They were asked to use clinical features to categorize lesions as low (LR), intermediate (IR), or high (HR) risk and then to determine FV status of these lesions. Clinicians made the decision of which lesions to reassess in 3 weeks and based on this reassessment, to refer forward. RESULTS: Of 2404 patients screened over 11 months, 357 initially had lesions with 325 (15%) identified as LR, 16 (4.5%) IR, and 16 (4.5%) HR. Lesions assessed initially as IR and HR had a 2.7-fold increased risk of FV loss persisting to the reassessment appointment versus the LR lesions. The most predictive model for lesion persistence included both FV status and lesion risk assessment. CONCLUSION: A protocol for screening (assess risk, reassess, and refer) is recommended for the screening of abnormal intraoral lesions. Integrating FV into a process of assessing and reassessing lesions significantly improved this model.

Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care centre.

BACKGROUND: We sought to evaluate the adequacy of follow-up of thyroid cancer patients at a Canadian centre. METHODS: We mailed a survey to the family physicians of thyroid cancer patients and analyzed the findings relative to follow-up guidelines published by the American Thyroid Association (ATA). Statistical significance between early and late follow-up patterns was analyzed using the χ(2) test. RESULTS: Our survey response rate was 56.2% (91 of 162). The time from operation ranged from 1.24-7.13 (mean 3.96) years, and 87.9% of patients had undergone a physical exam within the previous year. Only 37.4% and 14% of patients had a serum thyroglobulin measurement within 6 and between 6 and 12 months before the survey, respectively. Thyroid simulating hormone (TSH) levels were measured within the prior 6 months in 67% of patients and between 6 and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 µIU/L) in 24.2% of patients, 0.1-2 µIU/L in 44% and greater than 2 µIU/L in 17.6%. Ultrasonography was the most common imaging test performed. CONCLUSION: There is significant variation in the follow-up patterns of patients with thyroid cancer, and there is considerable deviation from current ATA guidelines.

CONTEXTE: Nous avons évalué la pertinence du suivi des patients atteints d'un cancer de la thyroïde dans un centre canadien. MÉTHODES: Nous avons posté un questionnaire aux médecins de famille de patients atteints d'un cancer de la thyroïde et analysé les résultats en regard des lignes directrices concernant le suivi publiées par l'American Thyroid Association (ATA). Nous avons utilisé le test du χ2 pour comparer la portée statistique des modes de suivi précoce et tardif. RÉSULTATS: Le taux de réponse à notre sondage a été de 56,2 % (91 sur 162). Le temps écoulé depuis l'intervention variait de 1,24 à 7,13 (moyenne 3,96) ans et 87,9 % des patients avaient subi un examen physique au cours de l'année écoulée. Seulement 37,4 % et 14 % des patients avaient eu un dosage de leur thyroglobuline sérique dans les derniers 6 mois et entre les 6e et 12e mois précédant le sondage, respectivement. Les taux de thyréostimuline (TSH) avaient été contrôlés au cours des 6 mois précédents chez 6 % des patients et entre les 6e et 12e mois chez 13,2 %. Les taux de TSH étaient supprimés (< 0,1 µUI/L) chez 24,2 % des patients, à 0,1­2 µUI/L chez 44 % et à plus de 2 µUI/L chez 17,6 %. L'échographie a été la technique d'ima gerie la plus utilisée. CONCLUSION: On note une variation significative dans le mode de suivi des patients atteints d'un cancer de la thyroïde et on note un écart considérable par rapport aux lignes directrices courantes de l'ATA.

Synoptic pathology reporting for thyroid cancer: a review and institutional experience.

Thyroid cancer surgical pathology reports contain information that is critical for diagnosis, determining completeness of resection, staging and guiding postoperative management. Traditional narrative pathology reporting is prone to errors and omissions with variability in content and completeness. The objective of this review was to evaluate the impact of synoptic reporting on thyroid cancer pathology reporting. Our institutional study of pathology reporting of differentiated thyroid cancers at a Canadian tertiary care institution relative to the College of American Pathologists checklists is also presented and critically evaluates deficiencies in the narrative pathology reporting format.

Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction.

The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.

Stage, treatment and outcomes for patients with breast cancer in British Columbia in 2002: a population-based cohort study.

BACKGROUND: There are very few long-term Canadian data on breast cancer outcomes by stage. We described the stage, treatment and outcomes of breast cancer at a population level for patients in British Columbia. METHODS: This population-based cohort study included almost all patients with incident breast cancer registered in 2002 (about 97.6% registry case completeness). For these patients, information on stage, primary local surgery, radiotherapy, chemotherapy, hormone therapy and survival outcome (based on registry date and cause-of-death data) were available. We calculated Kaplan-Meier curves for breast cancer-specific survival and overall survival by stage and analyzed prognostic and treatment factors with a multivariable Cox model. RESULTS: The 2927 incident cases of breast cancer identified in 2002 had the following distribution by stage: stage 0 (in situ), 424 (14%); stage I, 1118 (38%); stage II, 938 (32%); stage III, 233 (8%); stage IV, 123 (4%); unknown, 91 (3%). The distribution of patients' ages was < 40 years, 127 (4%); 40-49, 538 (18%); 50-59, 719 (25%); 60-69, 660 (23%); 70-79, 583 (20%); ≥ 80, 300 (10%). Within the first year after diagnosis, radiotherapy was provided to 1649 patients (56%), chemotherapy to 928 (32%) and hormone therapy to 1664 (57%). Ten-year breast cancer-specific survival rates by stage were > 99% for stage 0, 95% for stage I, 81% for stage II, 55% for stage III and 4% for stage IV. Ten-year overall survival rates were 89% for stage 0, 81% for stage I, 68% for stage II, 43% for stage III and 2% for stage IV. INTERPRETATION: This analysis provides a Canadian benchmark for treatment rates and 10-year outcomes by stage for all incident cases of breast cancer in a single province. Outcomes in British Columbia compared well with published rates for the United States and Europe.

Breast Cancer Survival Analysis: Applying the Generalized Gamma Distribution under Different Conditions of the Proportional Hazards and Accelerated Failure Time Assumptions.

BACKGROUND: The goal of this study is to extend the applications of parametric survival models so that they include cases in which accelerated failure time (AFT) assumption is not satisfied, and examine parametric and semiparametric models under different proportional hazards (PH) and AFT assumptions. METHODS: The data for 12,531 women diagnosed with breast cancer in British Columbia, Canada, during 1990-1999 were divided into eight groups according to patients' ages and stage of disease, and each group was assumed to have different AFT and PH assumptions. For parametric models, we fitted the saturated generalized gamma (GG) distribution, and compared this with the conventional AFT model. Using a likelihood ratio statistic, both models were compared to the simpler forms including the Weibull and lognormal. For semiparametric models, either Cox's PH model or stratified Cox model was fitted according to the PH assumption and tested using Schoenfeld residuals. The GG family was compared to the log-logistic model using Akaike information criterion (AIC) and Baysian information criterion (BIC). RESULTS: When PH and AFT assumptions were satisfied, semiparametric and parametric models both provided valid descriptions of breast cancer patient survival. When PH assumption was not satisfied but AFT condition held, the parametric models performed better than the stratified Cox model. When neither the PH nor the AFT assumptions were met, the log normal distribution provided a reasonable fit. CONCLUSIONS: When both the PH and AFT assumptions are satisfied, the parametric and semiparametric models provide complementary information. When PH assumption is not satisfied, the parametric models should be considered, whether the AFT assumption is met or not.

Gender- and ethnicity-specific survival trends of oral cavity and oropharyngeal cancers in British Columbia.

INTRODUCTION: A shift in etiology of oral cancers has been associated with a rise in incidence for oropharyngeal cancers (OPC) and decrease for oral cavity cancers (OCC); however, there is limited information about population-based survival trends. We report epidemiological transitions in survival for both OPC and OCC from a population-based cancer registry, focusing upon gender and ethnic differences. METHODS: All primary oral cancers diagnosed between 1980 and 2005 were identified from the British Columbia Cancer Registry and regrouped into OPC and OCC by topographical subsites, time periods (1980-1993 and 1994-2005), stage at diagnosis, and ethnicity. Cases were then followed up to December 2009. Using gender-based analysis, actuarial life tables were used to calculate survival rates, which were compared using Kaplan-Meier curves and log-rank tests. RESULTS: For OPC, survival improved, significant for tonsil and base of tongue in men and marginally significant at base of tongue in women. This improvement occurred in spite of an increase in late-stage diagnosis for OPC in both genders. Interestingly, there was no difference in survival for early- and late-stage disease for OPC in men. For OCC, there was a decrease in survival for floor of mouth cancers in both genders although significant in women only. South Asians had the poorest survival for OCC in both genders. CONCLUSION: Survival for OPC improved, more dramatically in men than women, in spite of late-stage diagnosis and increasing nodal involvement. Given the poor survival rates and need for early detection, targeted OCC screening programs are required for South Asians.

Applying conventional and saturated generalized gamma distributions in parametric survival analysis of breast cancer.

BACKGROUND: The generalized gamma distribution statistics constitute an extensive family that contains nearly all of the most commonly used distributions including the exponential, Weibull and log normal. A saturated version of the model allows covariates having effects through all the parameters of survival time distribution. Accelerated failure-time models assume that only one parameter of the distribution depends on the covariates. METHODS: We fitted both the conventional GG model and the saturated form for each of its members including the Weibull and lognormal distribution; and compared them using likelihood ratios. To compare the selected parameter distribution with log logistic distribution which is a famous distribution in survival analysis that is not included in generalized gamma family, we used the Akaike information criterion (AIC; r=l(b)-2p). All models were fitted using data for 369 women age 50 years or more, diagnosed with stage IV breast cancer in BC during 1990-1999 and followed to 2010. RESULTS: In both conventional and saturated parametric models, the lognormal was the best candidate among the GG family members; also, the lognormal fitted better than log-logistic distribution. By the conventional GG model, the variables "surgery", "radiotherapy", "hormone therapy", "erposneg" and interaction between "hormone therapy" and "erposneg"are significant. In the AFT model, we estimated the relative time for these variables. By the saturated GG model, similar significant variables are selected. Estimating the relative times in different percentiles of extended model illustrate the pattern in which the relative survival time change during the time. CONCLUSIONS: The advantage of using the generalized gamma distribution is that it facilitates estimating a model with improved fit over the standard Weibull or log- normal distributions. Alternatively, the generalized F family of distributions might be considered, of which the generalized gamma distribution is a member and also includes the commonly used log-logistic distribution.

Cancer risk in multiple sclerosis: findings from British Columbia, Canada.

Findings regarding cancer risk in people with multiple sclerosis have been inconsistent and few studies have explored the possibility of diagnostic neglect. The influence of a relapsing-onset versus primary progressive course on cancer risk is unknown. We examined cancer risk and tumour size at diagnosis in a cohort of patients with multiple sclerosis compared to the general population and we explored the influence of disease course. Clinical data of patients with multiple sclerosis residing in British Columbia, Canada who visited a British Columbia multiple sclerosis clinic from 1980 to 2004 were linked to provincial cancer registry, vital statistics and health registration data. Patients were followed for incident cancers between onset of multiple sclerosis, and the earlier of emigration, death or study end (31 December 2007). Cancer incidence was compared with that in the age-, sex- and calendar year-matched population of British Columbia. Tumour size at diagnosis of breast, prostate, colorectal and lung cancers were compared with population controls, matched for cancer site, sex, age and calendar year at cancer diagnosis, using the stratified Wilcoxon test. There were 6820 patients included, with 110 666 person-years of follow-up. The standardized incidence ratio for all cancers was 0.86 (95% confidence interval: 0.78-0.94). Colorectal cancer risk was also significantly reduced (standardized incidence ratio: 0.56; 95% confidence interval: 0.37-0.81). Risk reductions were similar by sex and for relapsing-onset and primary progressive multiple sclerosis. Tumour size was larger than expected in the cohort (P = 0.04). Overall cancer risk was lower in patients with multiple sclerosis than in the age-, sex- and calendar year matched general population. The larger tumour sizes at cancer diagnosis suggested diagnostic neglect; this could have major implications for the health, well-being and longevity of people with multiple sclerosis.

Demographic and tumor characteristics of patients diagnosed with nonmelanoma skin cancer: 13-year retrospective study.

BACKGROUND: The incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is increasing worldwide; however, this varies by region. To date, there are limited data about trends of nonmelanoma skin cancer (NMSC) in Canada. OBJECTIVE: To determine the demographic and tumor characteristic changes in patients diagnosed with BCC and SCC from 1993 to 2005 in a dermatology practice in Vancouver, British Columbia. METHOD: A retrospective chart review was conducted on patients with biopsy-confirmed NMSC between 1993 and 2005. Demographic and tumor characteristics were documented for the first two incident BCCs and SCCs per patient, and a descriptive data analysis was undertaken. RESULTS: A total of 1,177 NMSCs were identified from 885 patient charts. The number of BCCs increased from 1993 to 2003 and then decreased until 2005. BCCs and SCCs were generally diagnosed in older people (60+ years); however, an important group of younger patients (20-39 years) was also diagnosed with BCCs. BCCs and SCCs were most commonly seen on the head and neck, but the leg was a common location for SCC in women. CONCLUSION: NMSC is prevalent in British Columbia. These results highlight the fact that NMSC can affect individuals younger than 40 years old. Prevention strategies are warranted to reduce the burden of NMSC in British Columbia.

Effect of community population size on breast cancer screening, stage distribution, treatment use and outcomes.

OBJECTIVE: Residents of rural communities have decreased access to cancer screening and treatments compared to urban residents, though use of resources and patient outcomes have not been assessed with a comprehensive population-based analysis. The objectives of this study were to investigate whether breast cancer screening and treatments were utilized less frequently in rural BC and whether this translated into differences in outcomes. METHODS: All patients diagnosed with breast cancer in British Columbia (BC) during 2002 were identified from the Cancer Registry and linked to the Screening Mammography database. Patient demographics, pathology, stage, treatments, mammography use and death data were abstracted. Patients were categorized as residing in large, small and rural local health authorities (LHAs) using Canadian census information. Use of resources and outcomes were compared across these LHA size categories. We hypothesized that mastectomy rates (instead of breast-conserving surgery) would be higher in rural areas, since breast conservation is standardly accompanied by adjuvant radiotherapy, which has limited availability in rural BC. In contrast we hypothesized that cancer screening and systemic therapy use would be similar, as they are more widely dispersed across BC. Exploratory analyses were performed to assess whether disparities in screening and treatment utilization translated into differences in survival. RESULTS: 2,869 breast cancer patients were included in our study. Patients from rural communities presented with more advanced disease (p=0.01). On multivariable analysis, patients from rural, compared to urban, LHAs were less likely to be screening mammography attendees (OR=0.62; p<0.001). Women from rural communities were less likely to undergo breast-conserving surgery (multivariable OR=0.47; p<0.001). There was no significant difference in use of chemotherapy (p=0.54) or hormonal therapy (p=0.36). The 5-year breast cancer-specific survival for large, small and rural LHAs was 90%, 88% and 86%, respectively (p=0.08), while overall survival was 84%, 81% and 77%, respectively (p=0.01). On multivariable analysis with 7.4 years of median follow-up, neither breast cancer-specific survival (HR=1.16; 0.76-1.76; p=0.49) nor overall survival (HR=1.25; 0.92-1.70; p=0.16) was significantly worse for patients from rural compared to large LHAs. CONCLUSION: There was a significant difference in screening mammography use, stage distribution and loco-regional treatments use by population size of LHA. After controlling for differences in patient and tumour factors by LHA, survival was not significantly different.

Adherence to dietary recommendations and risk of esophageal squamous cell carcinoma: a case-control study in Iran.

BACKGROUND/AIM: The Dietary Guidelines for Americans Adherence Index (DGAI) 2005 was developed to assess the contribution of dietary patterns to chronic disease risk. The objective of this study was to evaluate the association of dietary patterns as measured by the DGAI 2005 with the esophageal squamous cell carcinoma (ESCC) risk in Iran. METHODS: This case-control study was conducted on 50 ESCC cases and 100 hospital controls aged 40-75 years. Participants were interviewed using validated food frequency questionnaires and the DGAI score was calculated subsequently. RESULTS: Generally, the mean DGAI 2005 score for this population was low (9.54 ± 1.79) and the control group scored significantly higher compared to the ESCC cases (p < 0.001). Being in the highest tertile of DGAI scores reduced the risk of ESCC by 31%. Consumption of salty, peppery, and sour foods in combination increased the ESCC risk by 7.23%, followed by consumption of fried/barbecued meals (OR 3.79; 95% CI 1.10-5.44; p < 0.001) and high-temperature food/beverages (OR 3.68; 95% CI 1.20-8.99; p < 0.001). CONCLUSIONS: Consumption of a diet in accordance with dietary recommendations was associated with a lower risk of ESCC. Preventive strategies to reduce the ESCC risk in high-risk regions of the world should focus on overall dietary patterns and dietary habits in order to be effective.

A case-match study comparing unilateral with synchronous bilateral breast cancer outcomes.

PURPOSE: There is controversy about whether patients with synchronous bilateral breast cancer (SBBC) have similar or worse outcomes compared with patients with unilateral breast cancer. The purpose of this study was to determine whether survival outcomes for patients with SBBC can be estimated from the characteristics of their individual cancers. PATIENTS AND METHODS: Patients had invasive breast cancer, without metastases or inflammatory disease, diagnosed in British Columbia between 1989 and 2000. There were 207 cases with SBBC (diagnosed ≤ 2 months apart) and 15,497 with unilateral breast cancer. By using 10-year breast cancer-specific survival (BCSS) estimates, the higher-risk cancer of each SBBC case was determined and matched with three breast cancers from the unilateral cohort to select 621 high-risk matches. The priority sequence of matching the prognostic and predictive variables was positive lymph node number, primary tumor size, age, grade, lymphovascular invasion, estrogen receptor status, local therapy used, margin status, treating clinic, diagnosis year, and type of systemic therapy used. RESULTS: With a median follow-up of 10.2 years, the overall 10-year BCSS was significantly higher for the unilateral cohort (81%; 95% CI, 81% to 82%) than for the SBBC cases (71%; 95% CI, 63% to 77%). The SBBC cases had significantly higher mean age and stage at presentation. The 10-year BCSS was 74% (95% CI, 69% to 77%) for the high-risk matches. CONCLUSION: BCSS was not significantly different between the SBBC cases and their high-risk matches.

The prognostic effect of ethnicity for gastric and esophageal cancer: the population-based experience in British Columbia, Canada.

BACKGROUND: Gastric and esophageal cancers are among the most lethal human malignancies. Their epidemiology is geographically diverse. This study compares the survival of gastric and esophageal cancer patients among several ethnic groups including Chinese, South Asians, Iranians and Others in British Columbia (BC), Canada. METHODS: Data were obtained from the population-based BC Cancer Registry for patients diagnosed with invasive esophageal and gastric cancer between 1984 and 2006. The ethnicity of patients was estimated according to their names and categorized as Chinese, South Asian, Iranian or Other. Cox proportional hazards regression analysis was used to estimate the effect of ethnicity adjusted for patient sex and age, disease histology, tumor location, disease stage and treatment. RESULTS: The survival of gastric cancer patients was significantly different among ethnic groups. Chinese patients showed better survival compared to others in univariate and multivariate analysis. The survival of esophageal cancer patients was significantly different among ethnic groups when the data was analyzed by a univariate test (p = 0.029), but not in the Cox multivariate model adjusted for other patient and prognostic factors. CONCLUSIONS: Ethnicity may represent underlying genetic factors. Such factors could influence host-tumor interactions by altering the tumor's etiology and therefore its chance of spreading. Alternatively, genetic factors may determine response to treatments. Finally, ethnicity may represent non-genetic factors that affect survival. Differences in survival by ethnicity support the importance of ethnicity as a prognostic factor, and may provide clues for the future identification of genetic or lifestyle factors that underlie these observations.

Comparison of two diverse populations, British Columbia, Canada, and Ardabil, Iran, indicates several variables associated with gastric and esophageal cancer survival.

BACKGROUND: Geographic variation and temporal trends in the epidemiology of esophageal and gastric cancers vary according to both tumor morphology and organ subsite. This study compares 1-year survival of gastric and esophageal cancers between two distinct populations: British Columbia (BC), Canada, and Ardabil, Iran. METHODS: Data for invasive primary esophageal and gastric cancer patients were obtained from the population-based cancer registries for BC and Ardabil. The relative survival rate was calculated using WHO Statistical Information System (WHOSIS) life-tables for each country. Chi-square and Fisher's exact tests were used to compare survival differences between BC and Ardabil. T-tests, chi-square tests, and Fisher's exact test were used to compare patient characteristics and tumor factors between the populations. RESULTS: The overall 1-year age-standardized relative survivals for gastric cancer were 48% and 21% in BC and Ardabil, respectively (p < 0.01). The overall 1-year age-standardized relative survival for esophageal cancer was 33% and 17% in BC and Ardabil, respectively (p < 0.05). Overall and separately for each gender, age group, tumor location, and histology, there was greater 1-year survival of the gastric cancer patients in BC compared to Ardabil. For esophageal cancer; patients under age 65, patients with tumors in the middle or upper third of esophagus, and patients with squamous cell carcinoma had significantly better survival in BC than in Ardabil. CONCLUSION: Findings of this study point to differences in disease characteristics and patient factors, not solely differences in healthcare systems, as being responsible for the survival difference in these populations.

Comparison of Aalen's additive and Cox proportional hazards models for breast cancer survival: analysis of population- based data from British Columbia, Canada.

BACKGROUND: Regression models for survival data have traditionally been based on the Cox regression model. However, its validity relies heavily on assumption of proportional hazards. Another restriction of the Cox model is insufficiency in dealing with time-varying covariate effects, since the regression coefficients are assumed constant. These weaknesses have generated interest in alternative approaches and with Aalen's additive model, the effect of the covariates acts on an absolute rather than a relative scale. We here fit the Cox and Aalen's additive models to breast cancer data for comparison through practical application. METHODS: The data related to 14,826 women diagnosed with breast cancer in BC during 1990-1999 and followed to 2010. Plots of the Martingale Residual Process and Arja's Plot was used to assess the fit of the additive model. The Cox-Snell residuals, Martingale residuals and scaled Schoenfeld residuals were used to check the Cox model. RESULTS: In the category of patients younger than 65 years the proportional hazard assumption was satisfied. In this category, by the Cox model, the variables "stage", "surgery", "radiotherapy", "chemotherapy", "hormone therapy" and interaction between "stage" and "surgery" proved significant. In the same category, by the Aalen's additive model, similar significant variables are selected except for "hormone therapy". The sign of estimated coefficients from survival functions based on the both Cox and Aalen's additive models were alike although estimated coefficients in the two models differed from the viewpoint of magnitude. In the category of patients older than 65 years, the proportional hazard assumption was not satisfied, and the Stratified Cox model and Aalen's additive model gave similar results. CONCLUSIONS: Based on our findings, if the proportional hazard assumption is not satisfied, the Aalen's additive model is an appropriate alternative for the Cox model. If the proportional hazard assumption is satisfied, both models are appropriate. Generally, the two models give different pieces of information.

Breast cancer treatment and ethnicity in British Columbia, Canada.

BACKGROUND: Racial and ethnic disparities in breast cancer incidence, stage at diagnosis, survival and mortality are well documented; but few studies have reported on disparities in breast cancer treatment. This paper compares the treatment received by breast cancer patients in British Columbia (BC) for three ethnic groups and three time periods. Values for breast cancer treatments received in the BC general population are provided for reference. METHODS: Information on patients, tumour characteristics and treatment was obtained from BC Cancer Registry (BCCR) and BC Cancer Agency (BCCA) records. Treatment among ethnic groups was analyzed by stage at diagnosis and time period at diagnosis. Differences among the three ethnic groups were tested using chi-square tests, Fisher exact tests and a multivariate logistic model. RESULTS: There was no significant difference in overall surgery use for stage I and II disease between the ethnic groups, however there were significant differences when surgery with and without radiation were considered separately. These differences did not change significantly with time. Treatment with chemotherapy and hormone therapy did not differ among the minority groups. CONCLUSION: The description of treatment differences is the first step to guiding interventions that reduce ethnic disparities. Specific studies need to examine reasons for the observed differences and the influence of culture and beliefs.

Trends in oropharyngeal and oral cavity cancer incidence of human papillomavirus (HPV)-related and HPV-unrelated sites in a multicultural population: the British Columbia experience.

BACKGROUND: There is a growing recognition of the involvement of human papilloma virus infection in the etiology of head and neck cancers at some sites, mainly the base of the tongue, tonsils, and other oropharynx (hereafter termed oropharyngeal cancer). Other oral sites (hereafter termed oral cavity cancer [OCC]) show a stronger association with tobacco and alcohol. Little is known about the ethnic variation in incidence for these cancers. This study determined incidence rates of OCC and oropharyngeal cancer among South Asian, Chinese, and the general population in British Columbia, Canada. METHODS: Patients with OCC and oropharyngeal cancer diagnosed from 1980 to 2006 were identified through the British Columbia cancer registry, and surname lists were used to establish ethnicity. Age-adjusted incidence rates were determined for these cancers by sex, topographical site, and ethnicity, and temporal trends were examined. RESULTS: Age-adjusted incidence rates have been decreasing for OCC and increasing for oropharyngeal cancer in the general population for both sexes, with men having higher incidence rates than women. Ethnic differences were found, with the highest age-adjusted incidence rates for OCC for men in South Asians and for women in Chinese, and with the highest age-adjusted incidence rates for oropharyngeal cancer for men in Chinese and for women in the general population. Differences were also found for OCC topographical sites by sex and ethnicity. CONCLUSIONS: The incidence of oropharyngeal cancer has now surpassed OCC in the British Columbia male population. Ethnic minorities are at higher risk than the general population for both OCC and oropharyngeal cancer for men, and for OCC for women.

Ultraviolet radiation.

The major source of ultraviolet radiation is solar radiation or sunlight. However, exposure to artificial sources particularly through tanning salons is becoming more important in terms of human health effects, as use of these facilities by young people, has increased. The International Agency for Research on Cancer has noted that there is sufficient evidence from studies in animals and in man to establish ultraviolet radiation as a human carcinogen. Skin cancer has been the most commonly studied cancer site with respect to UV radiation. The nature and timing of sun exposure appear to be important determinants of both the degree of risk and the type of skin cancer. Cutaneous malignant melanoma and basal cell cancer are much more strongly related to measures of intermittent ultraviolet exposure (particularly those of childhood or adolescence) than to measures of cumulative exposure. In contrast, squamous cell cancer is more strongly related to constant or cumulative sun exposure. Lip cancer is causally related to lifetime sun exposure. It has been estimated that solar ultraviolet radiation accounts for approximately 93 percent of skin cancers and about half of lip cancers. This translates to approximately 4,500 life-threatening cancers (cutaneous malignant melanoma) per year in Canada, as well as 65,000 less serious cancers (basal cell cancer, squamous cell cancer and lip cancer). Appropriate clothing use, care not to sunburn and judicious use of sunscreens could prevent at least half of these and save approximately 450 lives per year. In addition, physician and public education programs can significantly increase the proportion of melanomas diagnosed early. Lesions that have not yet penetrated deeply are associated with a mortality rate of less than five percent. Several recent studies suggest a possible inverse relationship between ultraviolet radiation exposure and risk of non-Hodgkin lymphoma, colon, breast and prostate cancer, and investigators have speculated that this might be due to the higher serum levels of vitamin D stimulated by high lifetime sun exposure. Further, studies conducted within cohorts using stored pre-diagnostic serum suggest that those with high levels of vitamin D have lower incidence rates of a number of malignancies, particularly colon cancer. However, since serum vitamin D levels can be raised through the use of supplements without increasing risk for skin lip and other known UV-related cancers, changes to health policy with regard to exposure are not merited at this point. Further research is needed in this area.